PMID- 31028143
OWN - NLM
STAT- MEDLINE
DCOM- 20200330
LR  - 20200422
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 116
IP  - 20
DP  - 2019 May 14
TI  - Protect, modify, deprotect (PMD): A strategy for creating vaccines to elicit 
      antibodies targeting a specific epitope.
PG  - 9947-9952
LID - 10.1073/pnas.1822062116 [doi]
AB  - In creating vaccines against infectious agents, there is often a desire to direct 
      an immune response toward a particular conformational epitope on an antigen. We 
      present a method, called protect, modify, deprotect (PMD), to generate 
      immunogenic proteins aimed to direct a vaccine-induced antibody (Ab) response 
      toward an epitope defined by a specific monoclonal Ab (mAb). The mAb is used to 
      protect the target epitope on the protein. Then the remaining exposed surfaces of 
      the protein are modified to render them nonimmunogenic. Finally, the epitope is 
      deprotected by removal of the mAb. The resultant protein is modified at surfaces 
      other than the target epitope. We validate PMD using a well-characterized 
      antigen, hen egg white lysozyme, then demonstrate the utility of PMD using 
      influenza virus hemagglutinin (HA). We use an mAb to protect a highly conserved 
      epitope on the stem domain of HA. Exposed surface amines are then modified with 
      short polyethylene glycol chains. The resultant antigen shows markedly reduced 
      binding to mAbs that target the head region of HA, while maintaining binding to 
      mAbs at the epitope of interest. This antigenic preference is also observed with 
      yeast cells displaying Ab fragments. Antisera from guinea pigs immunized with the 
      PMD-modified HA show increased cross-reactivity with HAs from other influenza 
      strains, compared with antisera obtained with unmodified HA trimers. PMD has the 
      potential to direct an Ab response at high resolution and could be used in 
      combination with other such strategies. There are many attractive targets for the 
      application of PMD.
CI  - Copyright (c) 2019 the Author(s). Published by PNAS.
FAU - Weidenbacher, Payton A
AU  - Weidenbacher PA
AD  - Stanford ChEM-H, Stanford University, Stanford, CA 94305.
AD  - Department of Chemistry, Stanford University, Stanford, CA 94305.
FAU - Kim, Peter S
AU  - Kim PS
AD  - Stanford ChEM-H, Stanford University, Stanford, CA 94305; kimpeter@stanford.edu.
AD  - Department of Biochemistry, School of Medicine, Stanford University, Stanford, CA 
      94305.
AD  - Chan Zuckerberg Biohub, San Francisco, CA 94158.
LA  - eng
GR  - T32 GM120007/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20190426
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Epitopes)
RN  - 0 (Hemagglutinin Glycoproteins, Influenza Virus)
RN  - 0 (Vaccines)
RN  - EC 3.2.1.17 (Muramidase)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal
MH  - Epitopes/*immunology
MH  - Guinea Pigs
MH  - Hemagglutinin Glycoproteins, Influenza Virus/immunology
MH  - *Immunogenicity, Vaccine
MH  - Muramidase/immunology
MH  - Vaccines/*immunology
PMC - PMC6525525
OTO - NOTNLM
OT  - antibodies
OT  - hemagglutinin
OT  - immunofocusing
OT  - influenza
OT  - vaccine
COIS- The authors declare no conflict of interest.
EDAT- 2019/04/28 06:00
MHDA- 2020/03/31 06:00
PMCR- 2019/04/26
CRDT- 2019/04/28 06:00
PHST- 2019/04/28 06:00 [pubmed]
PHST- 2020/03/31 06:00 [medline]
PHST- 2019/04/28 06:00 [entrez]
PHST- 2019/04/26 00:00 [pmc-release]
AID - 1822062116 [pii]
AID - 201822062 [pii]
AID - 10.1073/pnas.1822062116 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2019 May 14;116(20):9947-9952. doi: 
      10.1073/pnas.1822062116. Epub 2019 Apr 26.